A new pollen-derived microcarrier for pantoprazole delivery.

Plant-derived carriers have emerged as promising materials for drug encapsulation. Especially, sporopollenin microcapsules extracted from diverse pollen species have been proved to be effective drug carriers due to their biocompatibility, homogeneity in size, resistance to harsh chemical conditions and high thermal stability. Here in this study, sporopollenin microcapsules were isolated successfully from the pollens of a common tree (Corylus avellana, the European hazelnut) and used as a carrier for pantoprazole (PaNa) (a proton pump inhibitor). The drug entrapment efficiency was recorded as 29.81%. SEM micrographs clearly showed the drug was loaded into the microcapsules through the apertures of microcapsule and also some drugs were adsorbed on the surface of microcapsules. FT-IR spectra analysis confirmed the drug loading. Thermogravimetric analysis revealed that thermal stability of PaNa was enhanced by encapsulation. In vitro release studies showed that PaNa-loaded sporopollenin microcapsules exhibited better release performance than the control. C. avellana sporopollenin microcapsules can make an efficient carrier for delivery of PaNa.

[Proton Pump Inhibitor and High-dose Methotrexate: Two Cases Reports]. / Inhibiteurs de pompe à proton et méthotrexate haute dose : à propos de deux cas.

Methotrexate (MTX) is a cytotoxic agent prescribed at high dose in treatment of malignancy. Association of MTX to proton pump inhibitor (PPI) is not recommended if doses are more than 20 mg per weeks and only to take into account for smaller doses. Review relate some cases of delayed elimination of methotrexate in patients taking PPI, which increase risk of toxic event. However, currently there is no status quo on interaction between PPI and MTX according to available data. We report two clinical cases illustrating one more time a toxic event to MTX in presence of PPI. In absence of risk/benefit ratio set correctly, an assessment of appropriateness of PPI prescription before MTX therapy can limit an iatrogenic risk.

The pharmacokinetics of ilaprazole for gastro-esophageal reflux treatment.

INTRODUCTION: Approximately 20% of the Western population is affected by gastro-esophageal reflux disease (GERD). To date, proton pump inhibitors (PPIs) represent the mainstay of GERD medical treatment. However, despite their undoubted benefit, about 40% of GERD patients display an inadequate response to these drugs. Recently, a new PPI, ilaprazole , at oral doses of 10 mg has shown higher suppression of gastric acid secretion, more prolonged plasma half-life, and similar safety compared to 20 mg omeprazole. AREAS COVERED: This review provides an update on the following points: pharmacokinetic profile and metabolism of ilaprazole in relation to its pharmacodynamic properties; comparative data on the pharmacokinetics and pharmacodynamics of ilaprazole with currently available PPIs; and implications for studies on the therapeutic efficacy of ilaprazole in GERD. EXPERT OPINION: Different studies show that ilaprazole, a benzimidazole derivative, has an extended plasma half-life in comparison with all other approved PPIs. In addition, ilaprazole metabolism is not significantly influenced by CYP2C19, compared to the available PPIs. Furthermore, the pharmacological characteristics of ilaprazole confer theoretical advantages that are expected to translate into an improved acid control, particularly at night time. However, studies comparing the clinical pharmacokinetics and pharmacodynamics of ilaprazole with those of second-generation PPIs are insufficient. Moreover, further investigations assessing the efficacy of ilaprazole in the management of GERD are required. In healthy volunteers, as well as in patients with gastric or duodenal ulcers, ilaprazole has not shown clinically relevant changes in hematology and biochemistry testing, nor significant treatment-related adverse symptoms.

In vitro release profile of anti-ulcer drug rabeprazole from biocompatible psyllium-PVA hydrogels.

The present article discusses the synthesis, characterization and haemocompatibility behaviour of the psyllium-PVA hydrogels prepared by chemical method in the presence of N,N'-methylenebisacrylamide. These hydrogels have been characterized by Fourier Transform infrared spectroscopy, thermo gravimetric analysis, swelling and drug release studies. The release of model drug rabeprazole sodium from the drug loaded hydrogels occurred through non-Fickian diffusion mechanism. Psyllium itself acts as anti-ulcer agent and release of rabeprazole from the drug loaded hydrogels may enhance the curing potential of the drug delivery device. The haemocompatibility was evaluated by studying the blood interactions with hydrogels with reference to thrombogenicity and haemolytic potential. Thrombogenicity results indicate that hydrogels are non-thrombogenic as the weight of clot formed and thrombus percentage for hydrogels was less than the positive control. The haemolytic index has been observed <5%. These observations indicate that these hydrogels are haemo-compatible and hence could be used for oral administration of antiulcer drugs.

Influence of different proton pump inhibitors on activity of cytochrome P450 assessed by [(13)C]-aminopyrine breath test.

Aminopyrine is metabolized by cytochrome P450 (CYP) in the liver. The investigators evaluated influences of different PPIs on CYP activity as assessed by the [(13)C]-aminopyrine breath test ([(13)C]-ABT). Subjects were 15 healthy volunteers with different CYP2C19 status (5 rapid metabolizers [RMs], 5 intermediate metabolizers [IMs], and 5 poor metabolizers [PMs]). Breath samples were collected before and every 15 to 30 minutes for 3 hours after oral ingestion of [(13)C]-aminopyrine 100 mg on day 8 of each of the following regimens: control; omeprazole 20 mg and 80 mg, lansoprazole 30 mg, and rabeprazole 20 mg. Changes in carbon isotope ratios in carbon dioxide ((13)CO(2)/(12)CO(2)) in breath samples were measured by infrared spectrometry and expressed as delta-over-baseline (DOB) ratios (‰). Mean areas under the curve of DOB from 0 to 3 h (AUC(0-3h) of DOB) were significantly decreased by omeprazole 20 mg and lansoprazole 30 mg but not by rabeprazole 20 mg. Conversely, higher PPI dose (ie, omeprazole 80 mg) seemed to further decrease AUC(0-3h) of DOB in RMs but increased it in PMs. Omeprazole and lansoprazole at the standard doses inhibit CYP activity but rabeprazole does not, whereas high-dose omeprazole seems to induce CYPs.

[Microdialysis and HPLC method for determination of concentration of pantoprazole in rat striatum aftercombined administration with borneol].

OBJECTIVE: To observe the influence of borneol, a traditional Chinese medicine, on the concentration of ceftriaxone in the rat brain striatum and evaluate the relativity. METHOD: The sample of cerebrospinal fluid in the rat brain striatum was collected via brain microdialysis technology, and then the contents of ceftriaxone in standard preparation and sample were detected by high efficiency liquid chromatography combined with diode array detector respectively and analyzed statistically. The concentration of ceftriaxone in rat brain striatum in the ceftriaxone + Borneol group was compared with that in the ceftriaxone-only group. RESULT: The concentration of ceftriaxone in the rat brain in the ceftriaxone + Borneol group (13.01-4.43 mg x L(-1)) is significantly higher than that in the ceftriaxone-only group (2.41-0.94 mg x L(-1)). CONCLUSION: Borneol can promote ceftriaxone through blood-brain barrier, and increase the concentration thereof in striatum.

Efficacy and pharmacokinetics of pantoprazole in alpacas.

BACKGROUND: Despite frequent clinical use, information about the pharmacokinetics and efficacy of pantoprazole in camelids is not available. OBJECTIVES: To examine the pharmacokinetics of both IV and SC pantoprazole and to determine whether pantoprazole administration would increase 3rd compartment pH in alpacas. ANIMALS: Six healthy adult alpacas. METHODS: Alpacas were fitted with a 3rd compartment cannula for measuring gastric pH. After recovery, alpacas received 1 mg/kg pantoprazole IV, q24h for 3 days or 2 mg/kg SC q24h for 3 days. Alpacas received both IV and SC pantoprazole, with a minimum of 3 weeks between treatments. Third compartment pH was recorded and plasma samples were taken for pharmacokinetic analysis. RESULTS: Pantoprazole induced a slow but sustained increase in 3rd compartment pH when given by both the IV and SC routes. Third compartment pH was significantly increased as compared with baseline values (1.81+/-0.7; mean+/-SD) at 24 (2.47+/-0.8), 48 (3.53+/-1.0) and 72 hours (4.03+/-1.3) after daily IV administration of pantoprazole. Third compartment pH increased from 1.73+/-0.6 at baseline to 3.05+/-1.1, 4.02+/-1.4, and 3.61+/-1.6 at 24, 48, and 72 hours after SC administration, respectively. Pharmacokinetic analysis demonstrated that pantoprazole had a short elimination half-life (0.47+0.06 h) and a high clearance rate (12.2+/-2.9 mL/kg/min) after both IV and SC administration. CONCLUSIONS AND CLINICAL RELEVANCE: Based on the results of this study, pantoprazole represents a safe and effective drug for increasing 3rd compartment pH in camelids. Either IV or SC administration is likely to be an effective treatment for gastric ulcers.